A Novel Role for the Calcium Sensing Receptor in Rat Diabetic Encephalopathy
A Novel Role for the Calcium Sensing Receptor in Rat Diabetic Encephalopathy
复制标题
钙敏感受体在大鼠糖尿病脑病中的新作用
DOI：
10.1159/000369673
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Zhang, Weihua
中科院分区：
文献类型：
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作者：
Dong, Shiyun;Li, Gang;Zhang, Weihua
背景资料：糖尿病脑病是糖尿病常见的并发症，发病时可能与细胞内钙离子浓度（[Ca 2 +]i）改变有关。钙敏感受体（CaSR）是一种G蛋白偶联受体，但CaSR在糖尿病脑病中的作用尚不清楚。方法：采用链脲佐菌素（STZ，50 mg/kg）建立糖尿病大鼠模型。分别于第4、8、12周末用Western blot法检测海马CaSR的表达。在新生大鼠海马神经元中，激光扫描共聚焦显微镜检测[Ca 2 +]i，MitoSOX、DAF-FM和JC-1分别检测线粒体活性氧（ROS）产生、NO水平和线粒体跨膜电位。结果：在高糖处理的海马神经元中，CaSR通过PLC-IP 3途径调节[Ca 2 +]i。CaSR表达减少，并参与[Ca 2 +]i的变化。线粒体膜电位、NO释放和p-eNOS表达降低，而ROS产生增加。结论：CaSR表达下调伴随着神经元损伤、钙离子紊乱、ROS产生增加和NO释放减少。CaSR表达上调通过正性代偿保护机制减轻这些变化，抑制和延缓大鼠糖尿病脑病的发生。
Background: Diabetic encephalopathy is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations ([Ca2+]i) at its onset. The calcium sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic encephalopathy remains unclear. Methods: In this study, diabetic rats were modeled by STZ (50 mg/kg). At the end of 4, 8 and 12 weeks, the CaSR expression in hippocampus was analyzed by Western blot. In neonatal rat hippocampal neurons, the [Ca2+]i was detected by laser scanning confocal microscopy, the production of reactive oxygen species (ROS) in mitochondria, the level of NO and the mitochondrial transmembrane potential were measured by MitoSOX, DAF-FM and JC-1, respectively. Results: Our results showed in hippocampal neurons treated with high glucose, CaSR regulated [Ca2+]i through the PLC-IP3 pathway. CaSR expression was decreased and was involved in the changes in [Ca2+]i. Mitochondrial membrane potential, NO release and expression of p-eNOS decreased, while the production of ROS in mitochondria increased. Conclusion: Down-regulation of CaSR expression was accompanied by neuronal injury, calcium disturbance, increased ROS production and decreased release of NO. Up-regulation of CaSR expression attenuated these changes through a positive compensatory protective mechanism to inhibit and delay diabetic encephalopathy in rats.